Genes and obesity

Gnome writes "Obese people, defined as a body mass index (BMI) over 30 (weight/(height)^2 in kg/m^2), are at increased risk of disease (including type 2 diabetes, heart disease, stroke, some types of cancer) and death. Unlike risk that is clearly behavioral, such as smoking, or genetic, such as some BRCA alleles, obesity is itself caused by a combination of factors. Though the recent increase in obesity rates results largely from behavioral changes, BMI is partially heritable. Herbert and colleagues looked through the whole genome for common variants associated with obesity among participants in the Framingham Heart Study. They avoided the statistical problem of multiple comparisons by first screening using parental genotypes to identify SNPs and inheritance models that best predict offspring phenotypes and then performing a family based association test (FBAT, a type of transmission disequilibrium test (TDT)) to test the selected SNPs for their association with BMI. In step 1, they tested 116,204 SNPs in 694 participants. In step 2, the top 10 SNPs were tested using a recessive model, yielding only 1 significant SNP: rs7566605, which defines a single haplotype and is near INSIG2 (insulin-induced gene 2). “For all exams, rs7566605 CC homozygotes are about 1 BMI unit heavier than individuals with GC or GG genotypes (P <0.0001). They replicated this correlation in a cohort from a town near Munich, Germany, in a combination of Caucasian cohorts from Poland and the USA, and in two samples from an African American population from Illinois, USA. However, the rs7566605 SNP was not correlated with BMI among the Nurses Health Study cohort, perhaps because the cohort contained fewer individuals with a high BMI or because of differences in environment and lifestyle. This is one gene among several associated with obesity and leanness.
Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF. "A common genetic variant is associated with adult and childhood obesity." Science 2006; 312:279-83."Science. 2006 Apr 14;312(5771):279-83.